[LYMEINFO NOTE: Dr. Van Konynenburg is a proponent of the
Glutathione Depletion--Methylation Cycle Block hypothesis for the
pathogenesis of CFS. To read more about this theory and treatment, see
the links to the left of this page.]

1. The person inherits a genetic predisposition (polymorphisms
in several of certain genes) toward developing CFS. (This genetic
factor is more important for the sporadic cases than for the cluster
cases of CFS.)
2. The person then experiences some combination of a
variety
of possible stressors (physical, chemical, biological,
psychological/emotional) that place demands on glutathione.
3. Glutathione levels drop, producing oxidative stress,
removing protection from B12, allowing toxins to accumulate, and
shifting the immune response to Th2.
4. Toxins react with B12, lowering the rate of formation of
methylcobalamin. Lack of sufficient methylcobalamin inhibits methionine
synthase, placing a partial block in the methylation cycle.
5. Sulfur metabolites drain through the transsulfuration
pathway excessively, pass through sulfoxidation, and are excreted.
6. A vicious circle is established between the methylation
cycle block and glutathione depletion, and the disorder becomes chronic.

Depletion of glutathione by Borrelia burgdorferi

1. Bb requires cysteine for its metabolism [2].
2. Cysteine diffuses passively into Bb from its host, i.e.
there is no active transporter protein [2].
3. Bb uses cysteine in the synthesis of several of its
essential enzymes: Osp A, Osp B, CoASH, a hemolysin, and others [2,3].
4. Bb does not use glutathione for its redox control.
Instead, it uses reduced Coenzyme A (CoASH) [4].
5. Cysteine is the rate-limiting amino acid for the synthesis
of glutathione in humans, so that depletion of cysteine will produce
depletion of glutathione [5].
6. Bb lowers the cysteine and glutathione levels in its human
host, and inhibits the activity of glutathione peroxidase [6].
7. Low glutathione and low activity of glutathione peroxidase
allow a rise in hydrogen peroxide concentration and oxidative stress
[7].
8. Elevation of hydrogen peroxide causes Bb to assume its cyst
form [8], in which it is less vulnerable to antibiotics [9].

New hypothesis for a link between Lyme disease and chronic fatigue
syndrome

1. Borrelia burgdorferi (Bb) deplete glutathione in the host.
2. For a person who is genetically susceptible to developing
CFS, this provides a link to the GD-MCB hypothesis for CFS and is one of
the possible routes into this disorder.
3. If Bb and its biotoxin were not eliminated, Lyme disease
and CFS would coexist in the host, and this would constitute "chronic
Lyme disease."
4. If Bb and its biotoxin [10] were eliminated, but the
methylation cycle block continued, the person would continue to be ill
with CFS. This would constitute "post-Lyme disease syndrome," which
would be analogous to the other post-infective fatigue syndromes [11].
5. If Bb and its biotoxin were eliminated, and the methylation
cycle block was lifted, I believe it is likely that the person would
become well.

In addition,

6. Perhaps the Borrelia burgdorferi toxin is one of the toxins
that will
react with vitamin B12. Mold toxins have been implicated in such
reactions, but no data were cited [12,13].